NEJM Evidence publishes results from registrational PIONEER trial demonstrating significant clinical benefits of Ayvakit in indolent systemic mastocytosis

Ayvakit was designed to potently and selectively inhibit KIT D816V, the primary underlying driver of the disease. ISM represents the vast majority of cases of systemic mastocytosis (SM), a rare hematologic disorder that can lead to debilitating symptoms across multiple organ symptoms and a profound impact on patients' quality of life.

Highlights from the NEJM Evidence Publication: PIONEER is a randomized, double-blind, placebo-controlled trial in which 141 patients received Ayvakit 25 mg once daily plus best supportive care (Ayvakit) and 71 patients received placebo plus best supportive care (placebo). Disease symptoms were assessed using the ISM Symptom Assessment Form (ISM-SAF). As previously reported, Ayvakit met the primary and all key secondary endpoints, which were evaluated from baseline to 24 weeks, and showed deepening clinical efficacy through 48 weeks of treatment. Overall, 96 percent of patients with AYVAKIT completed 24 weeks of treatment and opted to cross over to the open-label extension study.

Key published results include: i. Patients treated with Ayvakit achieved rapid, durable and statistically significant reductions on all measures of pathological mast cell burden, including serum tryptase, KIT D816V variant allele fraction and bone marrow mast cells. ii. Ayvakit achieved statistically significant and clinically meaningful benefits in overall symptoms – as measured by the ISM-SAF Total Symptom Score (TSS) – compared to placebo at 24 weeks, with improvements deepening through 48 weeks. In addition, Ayvakit showed improvements over placebo on the most severe symptom and across all individual symptoms measured. iii. Ayvakit showed clinically meaningful improvements in multiple exploratory endpoints of quality of life, including a disease-specific measure – Mastocytosis Quality of Life Questionnaire (MC-QoL) – and general health status measures such as European Quality of Life Visual Analogue Scale (EQ-VAS), Patient Global Impression of Severity (PGIS) and 12-Item Short-Form Health Survey (SF-12). iv. Ayvakit showed a favorable safety profile, with most adverse events (AEs) mild to moderate in severity. The serious AE rate was 5.0 percent for Ayvakit and 11.3 percent for placebo. The most common treatment-emergent AEs for Ayvakit (incidence 5 percent and at least twice the rate of placebo) were flushing, edema, increased blood alkaline phosphatase and insomnia.

See- "Avapritinib versus Placebo in Indolent Systemic Mastocytosis": Authors: Jason Gotlib, M.D.. Mariana Castells, M.D., Ph.D., Hanneke Oude Elberink, M.D., Ph.D., Frank Siebenhaar, M.D., Karin Hartmann, M.D., et al., Published May 23, 2023 NEJM Evid 2023;2(6), DOI: 10.1056/EVIDoa2200339 VOL. 2 NO. 6.